G.I. Joe: Cobra Strike allows up to three players to play at the same time. The paddles control the two G.I. Joe guns, while the joystick controls the Cobra snake. As G.I. Joe, your mission is to protect the troops running across the bottom of the screen. Use the paddles to move your shield, blocking the snake's venom and laser beams. At the same time, you also need to shoot the snake in the eyes by pressing the fire button. Eight hits will destroy the snake allowing you to advance to the next level. If the Cobra snake hits four of your men, the game will end.
While players can battle the computer as G.I. Joe, the Cobra snake can only be controlled against human opponents. Playing as the Cobra snake, you must hit four of G.I. Joe's troops in order to win. If you are hit eight times, the game ends.